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. 1990 Jul;87(13):4942–4945. doi: 10.1073/pnas.87.13.4942

In vitro expression of rat lens aldose reductase in Escherichia coli.

S E Old 1, S Sato 1, P F Kador 1, D A Carper 1
PMCID: PMC54237  PMID: 2114645

Abstract

Aldose reductase (alditol:NADP+ oxidoreductase, EC 1.1.1.21), an enzyme that converts glucose to sorbitol, the first step of the polyol pathway, has been implicated in secondary complications of diabetes, such as cataracts, retinopathy, neuropathy, and nephropathy. Aldose reductase inhibitors have been observed to prevent or delay the onset of these complications; however, more potent and specific inhibitors are needed. Development of new inhibitors necessitates a better understanding of the molecular structure of this protein. To elucidate the structure-function relationships of aldose reductase and to develop methods of regulating this enzyme, large and homogeneous quantities of rat lens aldose reductase have been expressed in bacterial cells. A construction of the complete coding sequence and 3' untranslated region for rat lens aldose reductase was assembled in the expression vector pKK233-2 (Pharmacia). This construction expresses an active enzyme that has been purified and demonstrates kinetic, immunological, and inhibitory properties similar to rat lens aldose reductase.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akagi Y., Kador P. F., Kinoshita J. H. Immunohistochemical localization for aldose reductase in diabetic lenses. Invest Ophthalmol Vis Sci. 1987 Jan;28(1):163–167. [PubMed] [Google Scholar]
  2. Amann E., Brosius J., Ptashne M. Vectors bearing a hybrid trp-lac promoter useful for regulated expression of cloned genes in Escherichia coli. Gene. 1983 Nov;25(2-3):167–178. doi: 10.1016/0378-1119(83)90222-6. [DOI] [PubMed] [Google Scholar]
  3. Bagnasco S. M., Uchida S., Balaban R. S., Kador P. F., Burg M. B. Induction of aldose reductase and sorbitol in renal inner medullary cells by elevated extracellular NaCl. Proc Natl Acad Sci U S A. 1987 Mar;84(6):1718–1720. doi: 10.1073/pnas.84.6.1718. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bedford J. J., Bagnasco S. M., Kador P. F., Harris H. W., Jr, Burg M. B. Characterization and purification of a mammalian osmoregulatory protein, aldose reductase, induced in renal medullary cells by high extracellular NaCl. J Biol Chem. 1987 Oct 15;262(29):14255–14259. [PubMed] [Google Scholar]
  5. Bohren K. M., Bullock B., Wermuth B., Gabbay K. H. The aldo-keto reductase superfamily. cDNAs and deduced amino acid sequences of human aldehyde and aldose reductases. J Biol Chem. 1989 Jun 5;264(16):9547–9551. [PubMed] [Google Scholar]
  6. Bondy C. A., Lightman S. L. Developmental and physiological pattern of aldose reductase mRNA expression in lens and retina. Mol Endocrinol. 1989 Sep;3(9):1417–1425. doi: 10.1210/mend-3-9-1417. [DOI] [PubMed] [Google Scholar]
  7. Bondy C. A., Lightman S. L., Lightman S. L. Developmental and physiological regulation of aldose reductase mRNA expression in renal medulla. Mol Endocrinol. 1989 Sep;3(9):1409–1416. doi: 10.1210/mend-3-9-1409. [DOI] [PubMed] [Google Scholar]
  8. Burg M. B., Kador P. F. Sorbitol, osmoregulation, and the complications of diabetes. J Clin Invest. 1988 Mar;81(3):635–640. doi: 10.1172/JCI113366. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Carper D. A., Wistow G., Nishimura C., Graham C., Watanabe K., Fujii Y., Hayashi H., Hayaishi O. A superfamily of NADPH-dependent reductases in eukaryotes and prokaryotes. Exp Eye Res. 1989 Sep;49(3):377–388. doi: 10.1016/0014-4835(89)90048-1. [DOI] [PubMed] [Google Scholar]
  10. Carper D., Nishimura C., Shinohara T., Dietzchold B., Wistow G., Craft C., Kador P., Kinoshita J. H. Aldose reductase and p-crystallin belong to the same protein superfamily as aldehyde reductase. FEBS Lett. 1987 Aug 10;220(1):209–213. doi: 10.1016/0014-5793(87)80905-5. [DOI] [PubMed] [Google Scholar]
  11. Chung S., LaMendola J. Cloning and sequence determination of human placental aldose reductase gene. J Biol Chem. 1989 Sep 5;264(25):14775–14777. [PubMed] [Google Scholar]
  12. Chylack L. T., Jr, Tung W., Harding R. Sorbitol production in the lens: a means of counteracting glucose-derived osmotic stress. Ophthalmic Res. 1986;18(5):313–320. doi: 10.1159/000265455. [DOI] [PubMed] [Google Scholar]
  13. Gabbay K. H. The sorbitol pathway and the complications of diabetes. N Engl J Med. 1973 Apr 19;288(16):831–836. doi: 10.1056/NEJM197304192881609. [DOI] [PubMed] [Google Scholar]
  14. Garcia-Perez A., Martin B., Murphy H. R., Uchida S., Murer H., Cowley B. D., Jr, Handler J. S., Burg M. B. Molecular cloning of cDNA coding for kidney aldose reductase. Regulation of specific mRNA accumulation by NaCl-mediated osmotic stress. J Biol Chem. 1989 Oct 5;264(28):16815–16821. [PubMed] [Google Scholar]
  15. Herrmann R. K., Kador P. F., Kinoshita J. H. Rat lens aldose reductase: rapid purification and comparison with human placental aldose reductase. Exp Eye Res. 1983 Nov;37(5):467–474. doi: 10.1016/0014-4835(83)90022-2. [DOI] [PubMed] [Google Scholar]
  16. Judzewitsch R. G., Jaspan J. B., Polonsky K. S., Weinberg C. R., Halter J. B., Halar E., Pfeifer M. A., Vukadinovic C., Bernstein L., Schneider M. Aldose reductase inhibition improves nerve conduction velocity in diabetic patients. N Engl J Med. 1983 Jan 20;308(3):119–125. doi: 10.1056/NEJM198301203080302. [DOI] [PubMed] [Google Scholar]
  17. Kador P. F., Kinoshita J. H., Sharpless N. E. Aldose reductase inhibitors: a potential new class of agents for the pharmacological control of certain diabetic complications. J Med Chem. 1985 Jul;28(7):841–849. doi: 10.1021/jm00145a001. [DOI] [PubMed] [Google Scholar]
  18. Kador P. F. The role of aldose reductase in the development of diabetic complications. Med Res Rev. 1988 Jul-Sep;8(3):325–352. doi: 10.1002/med.2610080302. [DOI] [PubMed] [Google Scholar]
  19. Kinoshita J. H., Fukushi S., Kador P., Merola L. O. Aldose reductase in diabetic complications of the eye. Metabolism. 1979 Apr;28(4 Suppl 1):462–469. doi: 10.1016/0026-0495(79)90057-x. [DOI] [PubMed] [Google Scholar]
  20. Kinoshita J. H. Mechanisms initiating cataract formation. Proctor Lecture. Invest Ophthalmol. 1974 Oct;13(10):713–724. [PubMed] [Google Scholar]
  21. Robison W. G., Jr, Kador P. F., Akagi Y., Kinoshita J. H., Gonzalez R., Dvornik D. Prevention of basement membrane thickening in retinal capillaries by a novel inhibitor of aldose reductase, tolrestat. Diabetes. 1986 Mar;35(3):295–299. doi: 10.2337/diab.35.3.295. [DOI] [PubMed] [Google Scholar]
  22. Sato S., Kador P. F. Rat lens aldehyde reductase. Invest Ophthalmol Vis Sci. 1989 Jul;30(7):1618–1622. [PubMed] [Google Scholar]
  23. Stribling D., Mirrlees D. J., Harrison H. E., Earl D. C. Properties of ICI 128,436, a novel aldose reductase inhibitor, and its effects on diabetic complications in the rat. Metabolism. 1985 Apr;34(4):336–344. doi: 10.1016/0026-0495(85)90223-9. [DOI] [PubMed] [Google Scholar]

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